RT Journal Article SR Electronic T1 Widespread non-apoptotic activation of Drosophila Caspase-2/9 limits JNK signaling, macrophage proliferation, and growth of wound-like tumors JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.07.27.223404 DO 10.1101/2020.07.27.223404 A1 Derek Cui Xu A1 Kenneth M. Yamada A1 Luis Alberto Baena-Lopez YR 2020 UL http://biorxiv.org/content/early/2020/07/27/2020.07.27.223404.abstract AB Resistance to apoptosis due to caspase deregulation is considered one of the main hallmarks of cancer. However, the discovery of novel non-apoptotic caspase functions has revealed unknown intricacies about the interplay between these enzymes and tumor progression. To investigate this biological problem, we capitalized on a Drosophila tumor model highly relevant for humans that relies on the concomitant upregulation of EGFR and the JAK/STAT signaling pathway. Our results indicate that widespread non-apoptotic activation of initiator caspases limits JNK signaling and facilitates cell fate commitment in these tumors, thus preventing the overgrowth and exacerbation of malignant features. Intriguingly, these caspase functions are strongly linked to the ability of these enzymes to control the recruitment and subsequent proliferation in situ of macrophage-like cells on the tumor. These findings assign novel tumor-suppressor activities to caspases independent of apoptosis, while providing highly relevant molecular details to understanding their diverse contribution during tumor progression.Competing Interest StatementThe authors have declared no competing interest.